Project Title: Alpha-synuclein aggregates are targeted for degradation by phase-separated proteasome droplets
Supervisor: Dr Yu Ye, Professor Steve Gentleman
Location: Level 7, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ
About Me
I am a PhD student in the Department of Brain Sciences at Imperial College London, investigating the role of post-translational modifications of amyloid proteins in the pathogenesis of Alzheimer’s and Parkinson’s diseases. Prior to starting my PhD, I completed my BSc in Biochemistry at King's College London, MRes at Imperial, and worked as a research technician in the Kinases and Brain Development laboratory at The Francis Crick Institute.
Qualifications
- 2018-2019: MRes Molecular and Cellular Biosciences, Imperial College London
- 2015-2018: BSc Biochemistry, King’s College London
Research Interests
Post-translational modifications on amyloid proteins have been shown to have critical roles involved in their aggregation behaviour. Enhanced phosphorylation and ubiquitination have been found in tau tangles in Alzheimer’s disease (AD) and Lewy Bodies in Parkinson’s disease (PD). In addition, both ubiquitinating and deubiquitinating enzymes, as well as ubiquitin-dependent degradation through the proteasome, have been implicated in AD and PD. Understanding the key enzymatic activities that drive toxic protein aggregation is therefore critical to identify novel targets of therapeutic intervention to slow and reverse neurodegeneration.
The aim of my PhD project is to study how alpha-synuclein aggregates are targeted by proteasomes for degradation and why aggregates are not cleared in neurodegenerative diseases. My project combines biochemistry and cell biology approaches with advanced super-resolution microscopy techniques.
Publications
Morten M., Sirvio L., Rupawala H., Mee Hayes E., Franco Budia A., Radulescu C., Rupawala H., Ying L., Barnes SJ., Muga A., Ye Y. “Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.” Proceedings of the National Academy of Sciences, vol. 119, no. 41, 2022, https://doi.org/10.1073/pnas.2205591119
Mee Hayes E., Sirvio L., Ye Y. “A potential mechanism for targeting aggregates with proteasomes and disaggregases in liquid droplets.” Frontiers in Aging Neuroscience, vol. 14, 2022, https://doi.org/10.3389/fnagi.2022.854380
Presentations and conferences attended
- "Aggregates are Targeted for Degradation by Phase-Separated Proteasome Droplets" at the Stress Proteins in Growth, Development and Disease Gordon Research Seminar (GRS) - July 1-2, 2023
- Stress Proteins in Growth, Development and Disease Gordon Research Conference - July 2-7, 2023
Professional memberships
Biochemical Society
Contact Details
Email: les18@imperial.ac.uk
LinkedIn: liina-sirvio
How temperature and circadian rhythms intersect to regulate a protein shown to protect against neurodegeneration
A new study led by Dr Marco Brancaccio (UK DRI at Imperial) and Dr Marieke Hoekstra (former UK DRI at Imperial, now VIB-KU Leuven Center for Brain & Disease Research) offers a deeper insight into how a neuroprotective pathway is regulated both by temperature and the body clock. This research, published in the journal PNAS, could open up new therapeutic avenues for neurodegenerative disease. Read more on the UK DRI website
Introducing Cynthia Sandor: Pioneering earlier detection of Parkinson’s
Dr Cynthia Sandor, former Emerging Leader at the UK DRI at Cardiff, joins the UK DRI at Imperial as a Group Leader, where she will be tackling early diagnosis of Parkinson’s.
With a background in genetics, Dr Sandor uses computational methods to bring greater understanding to the underlying molecular mechanisms of Parkinson’s. Read more about Cynthia's work on the UK DRI website.
